Circumstantial evidence now exists to suggest an important role for central nervous system (CNS) epinephrine (Epi)-containing neurons in the regulation of cardiovascular function and thus in the genesis, development and/or maintainance of hypertension. The primary objective of this study will be to more extensively investigate from a biochemical and pharmacological standpoint, the role of CNS Epi in hypertension. This objective will be accomplished by determining the effects of acute and chronic alterations in blood pressure on brain Epi neuronal function in such animals. Brain Epi levels will be manipulated by designing and utilizing inhibitors of the biosynthetic enzyme, phenylethanolamine N-methyltransferase (PNMT); an approach which may be useful for the future design of antihypertensive agents.